Testosterone Restores Body Composition, Bone Mass, and Bone Strength Following Early Puberty Suppression in a Mouse Model Mimicking the Clinical Strategy in Trans Boys.

Autor: Dubois V; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.; Basic and Translational Endocrinology (BaTE), Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium., Ciancia S; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Doms S; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium., El Kharraz S; Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.; Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium., Sommers V; Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Kim NR; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium., David K; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium., Van Dijck J; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Valle-Tenney R; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Maes C; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Antonio L; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium., Decallonne B; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium., Carmeliet G; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium., Claessens F; Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Cools M; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.; Pediatric Endocrinology Service, Department of Pediatrics, Ghent University Hospital, Ghent, Belgium., Vanderschueren D; Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2023 Oct; Vol. 38 (10), pp. 1497-1508. Date of Electronic Publication: 2023 Jun 08.
DOI: 10.1002/jbmr.4832
Abstrakt: Transgender youth increasingly present at pediatric gender services. Some of them receive long-term puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) before starting gender-affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4-week-old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa-treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa-treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. © 2023 American Society for Bone and Mineral Research (ASBMR).
(© 2023 American Society for Bone and Mineral Research (ASBMR).)
Databáze: MEDLINE
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